1. 2015;18;E877-E887Is Serum Hypovitaminosis D Associated with Chronic Widespread Pain Including Fibromyalgia? A Meta-analysis of Observational Studies
   Observational Study
   Ming-Yen Hsiao, MD, Chen-Yu Hung, MD, Ke-Vin Chang, MD, Der-Sheng Han, MD, PhD, and Tyng-Guey Wang, MD.

BACKGROUND:  Chronic widespread pain (CWP) is a global musculoskeletal disorder leading to disability and a reduced quality of life. Low levels of serum vitamin D has long been proposed to be associated with CWP, but previous research remains inconclusive.
OBJECTIVES:  To determine whether hypovitaminosis D was independently associated with CWP.
STUDY DESIGN: Meta-analysis of observational study.
METHODS: Electronic databases were searched for studies published up to November 2014 comparing the prevalence of hypovitaminosis D and serum vitamin D levels between participants with and without CWP. The crude and adjusted odds ratios (ORs) of hypovitaminosis D with CWP were calculated. Subgroup analysis according to gender, threshold of hypovitaminosis, and definition of patients was performed, as well as meta-regression to test the linear relationship between crude ORs and the latitude of study locations.
RESULTS: Twelve studies were included, comprising 1,854 patients with CWP. The patient group showed a significantly higher risk of hypovitaminosis D than the control group (crude OR, 1.63; 95% CI, 1.20 – 2.23). The association was slightly attenuated after adjusting confounders, with a pooled adjusted OR of 1.41 (95% CI, 1.00 – 2.00). There was an increase in ORs of hypovitaminosis D using a lower diagnostic value of serum vitamin D (8 and 10 ng/mL). The subgroup analysis according to gender and definition of CWP did not reveal significant between-group differences. The meta-regression showed no linear relationship between latitude and the crude ORs.
CONCLUSIONS: There was a positive crude association between hypovitaminosis D and CWP, and the association was likely to remain after adjusting confounding factors. Use of a cut-off value of hypovitaminosis D (8 – 10 ng/mL) could better define the population with and without CWP. Further prospective follow-up studies are warranted to clarify the causal relationship between hypovitaminosis D and CWP.